GDF15 plays a critical role in insulin secretion in INS-1 cells and human pancreatic islets. 2023

Mohammad G Mohammad, and Rania Saeed, and Abdul Khader Mohammed, and Anila Khalique, and Mohamad Hamad, and Waseem El-Huneidi, and Mawieh Hamad, and Jalal Taneera
Department of Medical Laboratory Sciences, College of Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates (UAE).

Mounting evidence points to a link between growth differentiation factor-15 (GDF15) expression and the onset and progression of diabetes mellitus. However, the exact role of GDF15 in pancreatic β-cell function is unclear. To examine the role of GDF15 in β-cell function, bioinformatics analysis and functional experiments involving GDF15 silencing and overexpression were performed in INS-1 cells and human islets. Public microarray and RNA-seq expression data showed that islets obtained from diabetic donors express high levels of GDF15 compared to islets obtained from normal donors. Moreover, analysis of RNA-seq expression data revealed that GDF15 expression correlates positively with that of insulin (INS), KCNJ11, GLUT1, MAFA, INSR and negatively with that of Glucokinase (GCK) and Alpha-Ketoglutarate Dependent Dioxygenase (FTO). No T2D-associated genetic variants in the GDF15 were found to pass genome-wide significance in the TIGER portal. Expression silencing of Gdf15 in INS-1 cells reduced insulin release, glucose uptake levels, increased reactive oxygen species (ROS) production and apoptosis levels. While Gdf15-silenced cells downregulated mRNA expression of Ins, Pdx1, Mafa, and Glut2 genes, its overexpression human islets was associated with increased insulin secretion and upregulated expression of MAFA and GLUT1 but not INS or GCK. Silencing of Pdx1 or Mafa in INS-1 cells did not affect the expression of GDF15. These findings suggest that GDF15 plays a significant role in pancreatic β-cell function.

UI MeSH Term Description Entries
D007328 Insulin A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1). Iletin,Insulin A Chain,Insulin B Chain,Insulin, Regular,Novolin,Sodium Insulin,Soluble Insulin,Chain, Insulin B,Insulin, Sodium,Insulin, Soluble,Regular Insulin
D007515 Islets of Langerhans Irregular microscopic structures consisting of cords of endocrine cells that are scattered throughout the PANCREAS among the exocrine acini. Each islet is surrounded by connective tissue fibers and penetrated by a network of capillaries. There are four major cell types. The most abundant beta cells (50-80%) secrete INSULIN. Alpha cells (5-20%) secrete GLUCAGON. PP cells (10-35%) secrete PANCREATIC POLYPEPTIDE. Delta cells (~5%) secrete SOMATOSTATIN. Islands of Langerhans,Islet Cells,Nesidioblasts,Pancreas, Endocrine,Pancreatic Islets,Cell, Islet,Cells, Islet,Endocrine Pancreas,Islet Cell,Islet, Pancreatic,Islets, Pancreatic,Langerhans Islands,Langerhans Islets,Nesidioblast,Pancreatic Islet
D005947 Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Dextrose,Anhydrous Dextrose,D-Glucose,Glucose Monohydrate,Glucose, (DL)-Isomer,Glucose, (alpha-D)-Isomer,Glucose, (beta-D)-Isomer,D Glucose,Dextrose, Anhydrous,Monohydrate, Glucose
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000071516 Alpha-Ketoglutarate-Dependent Dioxygenase FTO A dioxygenase that repairs alkylated DNA and RNA by oxidative demethylation. It has highest activity towards single-stranded RNA containing 3-methyluracil, followed by SINGLE-STRANDED DNA containing 3-methylthymine and specifically demethylates N(6)-methyladenosine (m6A) RNA, the most common internal modification of MESSENGER RNA (mRNA) in higher EUKARYOTES. It contributes to the regulation of the global metabolic rate, energy HOMEOSTASIS, as well as body fat accumulation by regulating the differentiation of ADIPOCYTES into BROWN FAT CELLS or WHITE FAT CELLS. AlkB Homolog 9 Protein,Alpha-Ketoglutarate-Dependent Dioxygenase,Fat Mass and Obesity Associated (FTO) Protein,Fat Mass and Obesity Associated Protein,Alpha Ketoglutarate Dependent Dioxygenase,Alpha Ketoglutarate Dependent Dioxygenase FTO,Dioxygenase, Alpha-Ketoglutarate-Dependent,FTO, Alpha-Ketoglutarate-Dependent Dioxygenase
D000078790 Insulin Secretion Production and release of insulin from PANCREATIC BETA CELLS that primarily occurs in response to elevated BLOOD GLUCOSE levels. Secretion, Insulin
D050417 Insulin-Secreting Cells A type of pancreatic cell representing about 50-80% of the islet cells. Beta cells secrete INSULIN. Pancreatic beta Cells,beta Cells, Pancreatic,Pancreatic B Cells,B Cell, Pancreatic,B Cells, Pancreatic,Cell, Insulin-Secreting,Cells, Insulin-Secreting,Insulin Secreting Cells,Insulin-Secreting Cell,Pancreatic B Cell,Pancreatic beta Cell,beta Cell, Pancreatic
D051272 Glucose Transporter Type 1 A ubiquitously expressed glucose transporter that is important for constitutive, basal GLUCOSE transport. It is predominately expressed in ENDOTHELIAL CELLS and ERYTHROCYTES at the BLOOD-BRAIN BARRIER and is responsible for GLUCOSE entry into the BRAIN. Erythrocyte Glucose Transporter,GLUT-1 Protein,GLUT1 Protein,SLC2A1 Protein,Solute Carrier Family 2, Facilitated Glucose Transporter, Member 1 Protein,GLUT 1 Protein,Glucose Transporter, Erythrocyte
D055436 Growth Differentiation Factor 15 A growth differentiation factor that is secreted in response to cell stress and in response to MACROPHAGE ACTIVATION. In addition growth differentiation factor 15 demonstrates a diverse array of biological properties including the induction of cartilage formation, the inhibition of hematopoietic progenitor proliferation, and the induction of neuronal migration. GDF-15,Macrophage Inhibitory Cytokine 1,Prostate Differentiation Factor,Differentiation Factor, Prostate

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